ES2615236T3 - Treatment of viral infections - Google Patents
Treatment of viral infections Download PDFInfo
- Publication number
- ES2615236T3 ES2615236T3 ES12716630.4T ES12716630T ES2615236T3 ES 2615236 T3 ES2615236 T3 ES 2615236T3 ES 12716630 T ES12716630 T ES 12716630T ES 2615236 T3 ES2615236 T3 ES 2615236T3
- Authority
- ES
- Spain
- Prior art keywords
- composition according
- trichloroacetic acid
- acid
- cream
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Virology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Composición estable para el tratamiento de lesiones asociadas con infecciones víricas por herpes, donde la composición se encuentra en forma de cremas y geles que contienen una baja concentración de ácido tricloroacético, siendo la cantidad de ácido tricloroacético menor de un 6% (m/m) de la masa de la crema o gel.Stable composition for the treatment of lesions associated with herpes viral infections, where the composition is in the form of creams and gels that contain a low concentration of trichloroacetic acid, the amount of trichloroacetic acid being less than 6% (m / m) of the mass of the cream or gel.
Description
55
1010
15fifteen
20twenty
2525
3030
3535
4040
45Four. Five
50fifty
DESCRIPCIONDESCRIPTION
Tratamiento de infecciones vfricasTreatment of African infections
La presente invencion hace referencia al tratamiento o control de infecciones vfricas. En particular, pero no de forma exclusiva, la invencion hace referencia al tratamiento de infecciones vfricas del tipo herpes, incluyendo en particular herpes simple I, herpes simple II y herpes zoster.The present invention refers to the treatment or control of African infections. In particular, but not exclusively, the invention refers to the treatment of viral infections of the herpes type, including in particular herpes simplex I, herpes simplex II and herpes zoster.
El propio ser humano es el reservorio del herpesvirus hominis. Se ha descrito en un estudio que se han encontrado anticuerpos para el virus del herpes en un 30-37% de estudiantes universitarios, un 62% de pacientes privados y mas de un 80% de los pacientes de servicios ambulatorios. Aunque el virus se lleva como una infeccion latente en la mayorfa de los individuos, en otros tiene lugar una exacerbacion aguda del virus activado, de una variedad de formas, y puede precipitarse por una diversidad de factores, incluyendo factores traumaticos tales como la luz solar, la menstruacion, y contratiempos familiares. Se cree que las calenturas o ampollas labiales estan causadas por el herpes simple I, mientras que se cree que el herpes simple II es el agente en las infecciones de herpes genital.The human being himself is the reservoir of herpesvirus hominis. It has been described in a study that antibodies to the herpes virus have been found in 30-37% of university students, 62% of private patients and more than 80% of outpatient patients. Although the virus is carried as a latent infection in most individuals, in others an acute exacerbation of the activated virus occurs, in a variety of ways, and can be precipitated by a variety of factors, including traumatic factors such as sunlight , menstruation, and family setbacks. It is believed that cold sores or blisters are caused by herpes simplex I, while it is believed that herpes simplex II is the agent in genital herpes infections.
El herpes zoster (o simplemente zoster) causa la enfermedad de la piel comunmente conocida como culebrilla. Se trata de una enfermedad vfrica caracterizada por una erupcion cutanea dolorosa con ampollas en un area limitada en un costado del cuerpo, a menudo en forma de franja. La infeccion inicial con el virus de la varicela-zoster (VVZ) causa la enfermedad de la varicela aguda y de corta duracion, y ocurre habitualmente en ninos y jovenes. Una vez que un episodio de varicela se ha resuelto, el virus no se elimina del cuerpo sino que puede perdurar y causar culebrilla, la cual presenta diferentes sfntomas, a menudo muchos anos despues de la infeccion inicial.Herpes zoster (or simply zoster) causes the skin disease commonly known as shingles. It is a African disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in the form of a strip. Initial infection with the chickenpox-zoster virus (VZV) causes acute and short-lived chickenpox disease, and usually occurs in children and young people. Once an episode of chickenpox has resolved, the virus is not eliminated from the body but can last and cause shingles, which has different symptoms, often many years after the initial infection.
El virus de la varicela-zoster puede volverse latente en los cuerpos de celulas nerviosas, y menos frecuentemente en celulas satelite no neuronales del ganglio espinal, craneal o autonomico sin causar ningun sfntoma. En un individuo inmunocomprometido, quizas anos o decadas despues de la infeccion de varicela, el virus puede salir de los cuerpos celulares y se desplazan por los axones neuronales para causar infecciones vfricas de la piel en la region del nervio. El virus puede extenderse desde uno o mas ganglios a lo largo de los nervios de un segmento afectado e infectar el correspondiente dermatoma (un area de la piel suministrada por un nervio espinal), causando una erupcion dolorosa. Aunque la erupcion habitualmente se cura en un periodo de dos a cuatro semanas, algunas personas que sufren esta afeccion experimentan dolor residual del nervio durante meses o anos. Esta condicion se denomina neuralgia postherpetica. Exactamente no se entiende exactamente como el virus permanece latente en el organismo y posteriormente se re-activa.The varicella-zoster virus can become dormant in nerve cell bodies, and less frequently in non-neuronal satellite cells of the spinal, cranial, or autonomic ganglion without causing any symptoms. In an immunocompromised individual, perhaps years or decades after chickenpox infection, the virus can leave the cell bodies and travel through the neuronal axons to cause African skin infections in the nerve region. The virus can spread from one or more nodes along the nerves of an affected segment and infect the corresponding dermatome (an area of the skin supplied by a spinal nerve), causing a painful rash. Although the rash usually heals over a period of two to four weeks, some people who suffer from this condition experience residual nerve pain for months or years. This condition is called postherpetic neuralgia. Exactly it is not understood exactly how the virus remains latent in the organism and subsequently re-activates.
La tasa de incidencia mundial del herpes zoster se situa cada ano en un rango de 1,2 a 3,4 casos por cada 1.000 individuos sanos, aumentando a 3,9-11,8 por ano por cada 1.000 individuos entre aquellos mayores de 65 anos. El tratamiento con farmacos antivirales puede reducir la gravedad y la duracion del herpes zoster, si se comienza un tratamiento de siete a diez dfas de estos farmacos dentro de las 72 horas siguientes a la aparicion de la erupcion caracterfstica. El aminoacido lisina, que es un componente de las protefnas que tienen lugar en productos alimenticios naturales, se describe en la literatura como un agente anti-herpetico.The global incidence rate of herpes zoster is placed every year in a range of 1.2 to 3.4 cases per 1,000 healthy individuals, increasing to 3.9-11.8 per year per 1,000 individuals among those over 65 years. Treatment with antiviral drugs can reduce the severity and duration of herpes zoster, if a treatment of seven to ten days of these drugs is started within 72 hours after the onset of the characteristic rash. The amino acid lysine, which is a component of the proteins that take place in natural food products, is described in the literature as an anti-herpetic agent.
Una sorprendente caracterfstica de las infecciones por herpes es su aparicion en pacientes que se sabe que presentan un tftulo apreciable de anticuerpos del herpes. La presencia de anticuerpos no es, por tanto, una garantfa de proteccion contra brotes agudos. La via de infeccion del virus del herpes parece ser por contacto directo, tal como puede ocurrir entre parejas sexuales, madres e hijos e incluso paciente dentista.A striking feature of herpes infections is their appearance in patients known to have an appreciable titer of herpes antibodies. The presence of antibodies is therefore not a guarantee of protection against acute outbreaks. The route of infection of the herpes virus seems to be through direct contact, as can occur between sexual partners, mothers and children and even a dentist.
El herpes bucal puede tomar la forma de lesiones labiales recurrentes. Algunos pacientes presentan graves lesiones bucales que causan una considerable dificultad al comer. Se ha calculado que hasta un tercio de la poblacion presenta episodios recurrentes de infeccion bucal y que mas de la mitad de estos pacientes presentan mas de un episodio cada ano. Los virus del grupo del herpes tambien ocasionan enfermedad grave en pacientes que presentan deficiencias inmunologicas, por ejemplo pacientes con infecciones por VIH, y particularmente en pacientes que estan siendo tratados contra el cancer con farmacos con propiedades inmunosupresoras.Oral herpes can take the form of recurrent lip lesions. Some patients have severe oral lesions that cause considerable difficulty eating. It has been estimated that up to one third of the population has recurrent episodes of oral infection and that more than half of these patients have more than one episode each year. Herpes group viruses also cause serious illness in patients with immunological deficiencies, for example patients with HIV infections, and particularly in patients who are being treated for cancer with drugs with immunosuppressive properties.
El herpes ocular y la encefalitis herpetica son formas de infeccion adicionales con el virus del herpes que requieren una atencion medica intensiva y continuada que no incorpora el tratamiento descrito. El herpes genital, que tuvo una incidencia de 100.000 casos en los EE.UU. en 1973, se ha calculado que para 1980 habfa afectado al 30% de la poblacion sexualmente activa. El problema de las infecciones por herpes es por tanto un problema serio y creciente.Ocular herpes and herpetic encephalitis are additional forms of infection with the herpes virus that require intensive and continuous medical attention that does not incorporate the treatment described. Genital herpes, which had an incidence of 100,000 cases in the US In 1973, it was estimated that by 1980 it had affected 30% of the sexually active population. The problem of herpes infections is therefore a serious and growing problem.
La presente invencion proporciona el uso de acido tricloroacetico en la elaboracion de un medicamento para el tratamiento de infecciones vfricas mediante la administracion topica de una cantidad efectiva del medicamento a una persona o animal en necesidad de tratamiento.The present invention provides the use of trichloroacetic acid in the preparation of a medicament for the treatment of African infections by the topical administration of an effective amount of the medicament to a person or animal in need of treatment.
Las composiciones de acido tricloroacetico del arte previo se han presentado en forma de lfquidos o geles finos que se escurren facilmente tras su aplicacion. El solicitante conoce la memoria WO 00/71105(A2) (de Mezzoli), AcidoThe trichloroacetic acid compositions of the prior art have been presented in the form of liquids or fine gels that are easily drained after application. The applicant knows the report WO 00/71105 (A2) (from Mezzoli), Acid
55
1010
15fifteen
20twenty
2525
3030
3535
4040
45Four. Five
50fifty
5555
tricloroacetico para la preparacion de soluciones y/o composiciones para el tratamiento de lesiones erosivas y/o ulcerosas, que representa el arte previo mas cercano a la presente invencion conocido por el solicitante. Mezzoli describe el uso de soluciones acuosas de acido tricloroacetico para el tratamiento de lesiones erosivas y/o ulcerosas en las que las concentraciones de acido tricloroacetico en la solucion acuosa se encuentran en un rango de un mfnimo de un 10% a un maximo de un 90%, preferiblemente de un 10% a un 50% y mas preferiblemente de aproximadamente un 50%. Mezzoli indica (ver la pagina 5, lfneas 12 y 13) que las soluciones de acido tricloroacetico con concentraciones por debajo del 30% son inestables y han de ser utilizadas en un periodo muy corto de tiempo. Mezzoli tambien describe formulaciones de acido tricloroacetico en alcohol y eter, e indica que a mayor concentracion de acido tricloroacetico, mas activa es la solucion, mas corto es el periodo de tratamiento y de ahf menor el numero de aplicaciones topicas por dfa que se requiere. Mezzoli describe aplicaciones topicas que varfan de una a tres veces al dfa y describe que las lesiones ulcerosas aftosas menores desaparecen en un periodo de uno a tres dfas, y las lesiones se curan en un periodo de dos a cuatro dfas. En el caso de lesiones ulcerosas de aftas mayores, Mezzoli describe que el dolor y los signos de inflamacion desaparecen en un periodo de tres a cinco dfas y que la lesion se cura en un periodo de siete a ocho dfas. Las lesiones ulcerosas o erosivas de la membrana de la mucosa o del cutis tratadas de forma topica con el acido tricloroacetico lfquido de Mezzoli en solucion acuosa, o con composiciones farmaceuticas que comprenden el mismo, se vuelven blanquecinas debido a la accion del acido tricloroacetico en la lesion, y en la mucosa y el cutis alrededor de la lesion. La accion del acido tricloroacetico y el color blanquecino debido a la accion aumentan de intensidad con el aumento de la concentracion de acido tricloroacetico en la solucion acuosa o la composicion farmaceutica.trichloroacetic for the preparation of solutions and / or compositions for the treatment of erosive and / or ulcerative lesions, which represents the prior art closest to the present invention known to the applicant. Mezzoli describes the use of aqueous solutions of trichloroacetic acid for the treatment of erosive and / or ulcerative lesions in which the concentrations of trichloroacetic acid in the aqueous solution are in a range of a minimum of 10% to a maximum of 90 %, preferably from 10% to 50% and more preferably from about 50%. Mezzoli indicates (see page 5, lines 12 and 13) that trichloroacetic acid solutions with concentrations below 30% are unstable and must be used in a very short period of time. Mezzoli also describes formulations of trichloroacetic acid in alcohol and ether, and indicates that the higher the concentration of trichloroacetic acid, the more active the solution is, the shorter the treatment period and the smaller the number of topical applications per day required. Mezzoli describes topical applications that vary from one to three times a day and describes that minor aphthous ulcerative lesions disappear in a period of one to three days, and the lesions heal in a period of two to four days. In the case of ulcerative lesions of major sores, Mezzoli describes that the pain and signs of inflammation disappear in a period of three to five days and that the injury heals in a period of seven to eight days. Ulcerative or erosive lesions of the mucous membrane or complexion treated topically with Mezzoli liquid trichloroacetic acid in aqueous solution, or with pharmaceutical compositions comprising the same, become whitish due to the action of trichloroacetic acid in the lesion, and in the mucosa and complexion around the lesion. The action of the trichloroacetic acid and the whitish color due to the action increase in intensity with the increase in the concentration of trichloroacetic acid in the aqueous solution or the pharmaceutical composition.
La memoria WO 97/09963 divulga un metodo para tratar la piel de un paciente humano sin someter al paciente a radiacion luminosa. El metodo emplea una composicion que contiene acido tricloroacetico al 30% como maximo, un agente de visualizacion y un tensioactivo para tratar la piel de un paciente con descamacion en la piel.WO 97/09963 discloses a method for treating the skin of a human patient without subjecting the patient to light radiation. The method employs a composition containing a maximum of 30% trichloroacetic acid, a visualizing agent and a surfactant to treat the skin of a patient with skin peeling.
El solicitante ha observado en la actualidad, sorprendentemente, que una formulacion en forma de una crema o gel, que contiene solamente un 5% de acido tricloroacetico es muy efectiva para el tratamiento de lesiones de herpes a pesar de la creencia mantenida comunmente entre los expertos medicos que se ocupan del tratamiento de lesiones de ese tipo, de que una concentracion de acido tricloroacetico al 5% en una formulacion farmaceutica resultana ineficaz. Los resultados obtenidos con la formulacion de la presente invencion son por consiguiente inesperados, a la luz de la vision ampliamente mantenida de que las formulaciones que contienen bajas concentraciones de acido tricloroacetico serfan ineficaces para el tratamiento de lesiones del herpes.The applicant has observed, surprisingly, that a formulation in the form of a cream or gel, containing only 5% trichloroacetic acid is very effective for the treatment of herpes lesions despite the belief commonly held among experts doctors who deal with the treatment of such injuries, that a 5% trichloroacetic acid concentration in a pharmaceutical formulation is ineffective. The results obtained with the formulation of the present invention are therefore unexpected, in the light of the widely held view that formulations containing low concentrations of trichloroacetic acid would be ineffective for the treatment of herpes lesions.
Segun un primer aspecto de la invencion, se proporciona una composicion estable para el tratamiento de lesiones asociadas con infecciones de herpes vfrico, donde la composicion se encuentra en una forma seleccionada de entre cremas y geles y que contiene una baja concentracion de acido tricloroacetico, donde la cantidad de acido tricloroacetico es menor del 6% (m/m) de la masa de la crema o gel.According to a first aspect of the invention, a stable composition is provided for the treatment of lesions associated with viral herpes infections, where the composition is in a selected form between creams and gels and which contains a low concentration of trichloroacetic acid, where The amount of trichloroacetic acid is less than 6% (m / m) of the mass of the cream or gel.
La abreviatura "% (m/m)" hace referencia al porcentaje en masa del acido tricloroacetico en una masa determinada de la composicion. Por “baja concentracion” en el contexto de esta especificacion, se entiende una concentracion de acido tricloroacetico que es menor del 6% y, preferiblemente, entre aproximadamente un 2,5 y un 5% (m/m). Por “composicion estable” se entiende una composicion que es estable durante al menos 12-18 meses. Se habfa observado que las composiciones del arte previo que contenfan menos del 30% de acido tricloroacetico son sustancialmente menos estables, con una vida util en almacenamiento de menos de aproximadamente 6 meses.The abbreviation "% (m / m)" refers to the mass percentage of trichloroacetic acid in a given mass of the composition. By "low concentration" in the context of this specification, a trichloroacetic acid concentration is understood to be less than 6% and, preferably, between about 2.5 and 5% (m / m). By "stable composition" is meant a composition that is stable for at least 12-18 months. It had been observed that prior art compositions containing less than 30% trichloroacetic acid are substantially less stable, with a shelf life of less than about 6 months.
La cantidad de acido tricloroacetico puede estar entre aproximadamente un 1% y un 5,5% (m/m), preferiblemente entre aproximadamente un 1,5% y un 5% (m/m) y mas preferiblemente entre aproximadamente un 2,5% y un 5,0% (m/m). En un modo de realizacion preferido de la invencion, la composicion se encuentra en forma de crema y la cantidad de acido tricloroacetico en la crema es de aproximadamente un 5% (m/m). En otra realizacion preferida de la invencion, la composicion se encuentra en forma de gel y la cantidad de acido tricloroacetico en el gel es de aproximadamente un 2,5%.The amount of trichloroacetic acid may be between about 1% and 5.5% (m / m), preferably between about 1.5% and 5% (m / m) and more preferably between about 2.5 % and 5.0% (m / m). In a preferred embodiment of the invention, the composition is in the form of a cream and the amount of trichloroacetic acid in the cream is approximately 5% (m / m). In another preferred embodiment of the invention, the composition is in the form of a gel and the amount of trichloroacetic acid in the gel is approximately 2.5%.
Una ventaja de la composicion de la invencion es que la baja concentracion de acido tricloroacetico permitira que la composicion sea comercializada como un medicamento no sujeto a prescripcion medica que puede ser aplicado de forma segura por el comprador y que no requerira ser administrado por un terapeuta experto. Una segunda ventaja importante de la invencion es que debido a que la composicion se encuentra en forma de una crema o gel puede aplicarse facilmente y de forma precisa a una lesion. Las formulaciones del arte previo tales como la de Mezzoli, son fluidos o geles finos que no pueden aplicarse de forma precisa y que tienden a escurrirse y por lo tanto entran en contacto con la piel alrededor de la lesion. Debido a que estos lfquidos o geles finos presentan concentraciones de acido tricloroacetico que son mucho mas elevadas que la concentracion de la composicion de la invencion, afectan a la piel en el area alrededor de la lesion causando abrasion y descamacion. La composicion de la invencion puede aplicarse de forma precisa en una lesion y no se escurrira bajo la influencia de la gravedad, de manera que permanece en el lugar en el que se aplica durante la duracion del tratamiento. Debido a que puede aplicarse de forma precisa y que no se escurre, la composicion de la invencion generalmente necesita ser aplicada solamente una vez, a continuacion de lo cual la lesion se seca y rapidamente se cura con minima descamacion en un periodo de 24 a 48 horas. Las formulaciones del arte previo, tal como la formulacion de Mezzoli, requieren de uno a tresAn advantage of the composition of the invention is that the low concentration of trichloroacetic acid will allow the composition to be marketed as a medicament not subject to medical prescription that can be safely applied by the buyer and will not require to be administered by an expert therapist. . A second important advantage of the invention is that because the composition is in the form of a cream or gel it can be easily and accurately applied to an injury. Prior art formulations such as Mezzoli, are fine fluids or gels that cannot be applied precisely and tend to drain and therefore come into contact with the skin around the lesion. Because these liquids or fine gels have concentrations of trichloroacetic acid that are much higher than the concentration of the composition of the invention, they affect the skin in the area around the lesion causing abrasion and scaling. The composition of the invention can be applied precisely in an injury and will not be drained under the influence of gravity, so that it remains in the place where it is applied for the duration of the treatment. Because it can be applied precisely and does not drain, the composition of the invention generally needs to be applied only once, following which the lesion dries and quickly heals with minimal scaling over a period of 24 to 48 hours. Prior art formulations, such as the Mezzoli formulation, require one to three
tratamientos por dfa durante un periodo de dos a cuatro dfas, y se produce abrasion y descamacion alrededor de la lesion. El solicitante es un experto en el area de la invencion y sabe que el proceso de Mezzoli no ha resultado exitoso y serfa un proceso doloroso y muy inconveniente. El solicitante es tambien de la opinion de que las concentraciones mas elevadas de acido tricloroacetico evitarfan que las formulaciones de Mezzoli se vendieran 5 como medicamentos no sujetos a prescripcion medica.treatments per day for a period of two to four days, and abrasion and peeling around the injury occurs. The applicant is an expert in the area of the invention and knows that the Mezzoli process has not been successful and would be a painful and very inconvenient process. The applicant is also of the opinion that higher concentrations of trichloroacetic acid would prevent Mezzoli formulations from being sold as drugs not subject to medical prescription.
La composicion puede incluir excipientes farmaceuticamente aceptables, seleccionados de entre formadores de viscosidad, humectantes (o agentes humidificantes), emulsionantes, agentes quelantes o mezclas de los mismos. Los emulsionantes son componentes que ayudan a mantener las fases oleosa y acuosa estables en una emulsion tal como una crema.The composition may include pharmaceutically acceptable excipients, selected from viscosity formers, humectants (or humidifying agents), emulsifiers, chelating agents or mixtures thereof. Emulsifiers are components that help keep the oil and water phases stable in an emulsion such as a cream.
10 El formador de viscosidad puede seleccionarse de entre goma xantana, hidroxipropil guar, silicato de magnesio y aluminio, hidroxietilcelulosa y mezclas de dos o mas de los mismos. El humectante puede seleccionarse de entre propilenglicol, butilenglicol, pentilenglicol, glicerina, sorbitol y mezclas de dos o mas de los mismos. Los emulsionantes pueden seleccionarse de entre alcoholes grasos, eteres de polietilenglicol de acidos grasos, esteres de glicerol de acidos grasos de cadena larga, esteres de polietilenglicol de acidos grasos de cadena larga y mezclas 15 de los mismos. El agente quelante puede seleccionarse de entre acido etilendiaminotetraacetico (EDTA), preferiblemente como su sal sodica, diacetato de tetrasodio glutamato, acido etilendiamina-N,N'-disuccfnico (EDDS) y mezclas de dos o mas de los mismos.The viscosity former may be selected from xanthan gum, hydroxypropyl guar, magnesium aluminum silicate, hydroxyethylcellulose and mixtures of two or more thereof. The humectant may be selected from propylene glycol, butylene glycol, pentylene glycol, glycerin, sorbitol and mixtures of two or more thereof. The emulsifiers can be selected from fatty alcohols, polyethylene glycol ethers of fatty acids, glycerol esters of long chain fatty acids, polyethylene glycol esters of long chain fatty acids and mixtures thereof. The chelating agent may be selected from ethylenediaminetetraacetic acid (EDTA), preferably as its sodium salt, tetrasodium glutamate diacetate, ethylenediamine-N acid, N'-disuccinic acid (EDDS) and mixtures of two or more thereof.
El alcohol graso puede ser un alcohol C16-C18 tal como alcohol cetearflico (o cetostearflico) alcohol. El eter de polietilenglicol del alcohol graso puede ser ceteareth-20. El ester de glicerol puede ser estearato de glicerilo. El ester 20 de polietilenglicol puede ser estearato de oxido de polietileno tal como estearato de PEG-40.The fatty alcohol may be a C16-C18 alcohol such as cetearyl alcohol (or ketostearyl) alcohol. The polyethylene glycol ether of the fatty alcohol can be ceteareth-20. The glycerol ester may be glyceryl stearate. The polyethylene glycol ester 20 may be polyethylene oxide stearate such as PEG-40 stearate.
En una realizacion de la invencion, la composicion puede contener aproximadamente de un 0,5% a un 6,0% (m/m) de acido tricloroacetico, aproximadamente de un 5% a un 15% (m/m) del emulsionante, de aproximadamente un 0,2% a un 1,2% (m/m) de goma xantana, aproximadamente de un 1% a un 5% (m/m) de propilenglicol y aproximadamente de un 0,25% a un 0,35% (m/m) de EDTA como sal sodica.In one embodiment of the invention, the composition may contain approximately 0.5% to 6.0% (m / m) of trichloroacetic acid, approximately 5% to 15% (m / m) of the emulsifier, from about 0.2% to 1.2% (m / m) of xanthan gum, about 1% to 5% (m / m) of propylene glycol and about 0.25% to 0, 35% (m / m) of EDTA as sodium salt.
25 La composicion puede contener aproximadamente un 0,3% (m/m) de EDTA.The composition may contain approximately 0.3% (m / m) of EDTA.
En otra realizacion de la invencion, la composicion puede contener entre un 1,0% y un 5% (m/m) de acido tricloroacetico y puede ser utilizado en un gel con propiedades de secado lento.In another embodiment of the invention, the composition may contain between 1.0% and 5% (m / m) of trichloroacetic acid and may be used in a gel with slow drying properties.
La infeccion vfrica puede ser una infeccion por el virus del herpes y puede, en particular, ser una infeccion causada por el herpes simple I, herpes simple II o herpes zoster.The African infection may be an infection with the herpes virus and may, in particular, be an infection caused by herpes simplex I, herpes simplex II or herpes zoster.
30 El solicitante ha observado que el medicamento de la invencion es efectivo en el tratamiento de lesiones de los labios, boca, encfas, genitales, tronco y miembros cuando se aplica en forma de crema. El solicitante es consciente de que las infecciones por herpes pueden detenerse en las etapas iniciales bajando el pH de la piel a un valor de pH de aproximadamente 2. El solicitante tambien es consciente de que el acido tricloroacetico en concentraciones mas bajas se tolera bien por parte de los tejidos corporales, y los tejidos circundantes no resultan danados por una corta 35 exposicion al acido tricloroacetico. Paradojicamente, se sabe que concentraciones mas elevadas de acido tricloroacetico empeoran las infecciones por herpes. El solicitante ha observado en la actualidad que todas las lesiones por herpes se pueden tratar y pueden detenerse mediante la aplicacion de una composicion de acido tricloroacetico, tal como una crema que contiene entre un 1% y un 5% de acido tricloroacetico o un gel que contiene aproximadamente un 2,5% de acido tricloroacetico.30 The applicant has observed that the medicament of the invention is effective in the treatment of lesions of the lips, mouth, gums, genitals, trunk and limbs when applied as a cream. The applicant is aware that herpes infections can be stopped in the early stages by lowering the skin's pH to a pH value of approximately 2. The applicant is also aware that trichloroacetic acid at lower concentrations is well tolerated by of body tissues, and surrounding tissues are not damaged by a short exposure to trichloroacetic acid. Paradoxically, it is known that higher concentrations of trichloroacetic acid worsen herpes infections. The applicant has now observed that all herpes lesions can be treated and stopped by the application of a trichloroacetic acid composition, such as a cream containing between 1% and 5% trichloroacetic acid or a gel that It contains approximately 2.5% trichloroacetic acid.
40 Para una aplicacion topica, el acido tricloroacetico se dispersa preferiblemente en forma de un fino polvo en una base de crema convencional a una concentracion de entre aproximadamente un 0,5% y aproximadamente un 5% (m/m), preferiblemente aproximadamente un 5%. La crema se aplica libremente a las partes afectadas y se extiende frotando suavemente para que penetre en los tejidos. Las aplicaciones pueden realizarse una vez o, para infecciones graves, cada 12 horas durante uno a dos dfas. La forma en crema puede ser utilizada tambien para 45 aplicaciones topicas intrabucalmente e intravaginalmente. El solicitante sabe que el virus del herpes debe unirse en primer lugar a un receptor en la superficie de la celula antes de que pueda penetrarla. Esto requiere una alcalinizacion intra-celular, y si se produce un cambio del pH hacia la acidosis entonces el virus no puede unirse y replicarse. Esto evita que se extienda la infeccion. El solicitante cree que la dosis baja de acido tricloroacetico de la invencion funciona de este modo y proporciona un tratamiento eficaz, conveniente y rentable de una infeccion por el 50 virus del herpes. El cambio en el pH de la piel causado por la aplicacion topica del acido es en efecto responsable de los efectos terapeuticos.For a topical application, the trichloroacetic acid is preferably dispersed in the form of a fine powder in a conventional cream base at a concentration of between about 0.5% and about 5% (m / m), preferably about 5 %. The cream is freely applied to the affected parts and spread gently by rubbing it to penetrate the tissues. Applications can be made once or, for serious infections, every 12 hours for one to two days. The cream form can also be used for topical applications intrabucally and intravaginally. The applicant knows that the herpes virus must first bind to a receptor on the surface of the cell before it can penetrate it. This requires intra-cellular alkalinization, and if there is a change in pH towards acidosis then the virus cannot bind and replicate. This prevents the infection from spreading. The applicant believes that the low dose of trichloroacetic acid of the invention works in this way and provides an effective, convenient and cost-effective treatment of an infection with the herpes virus. The change in the pH of the skin caused by the topical application of the acid is in effect responsible for the therapeutic effects.
Las ventajas de la invencion pueden resumirse como sigue a continuacion. La formulacion de la invencion en primer lugar no es una solucion, sino una crema que puede ser utilizada facilmente y de forma segura por el consumidor final, mientras que las composiciones del arte previo son lfquidos que pueden ser utilizados unicamente por clfnicosThe advantages of the invention can be summarized as follows. The formulation of the invention in the first place is not a solution, but a cream that can be used easily and safely by the final consumer, while the compositions of the prior art are liquids that can only be used by clinicians.
55
1010
15fifteen
20twenty
2525
3030
3535
4040
45Four. Five
50fifty
5555
expertos. La crema de la invencion no causa dolor y como mucho causa una ligera sensacion de escozor mientras que la formulacion del arte previo escuece y produce abrasion en gran medida y puede ser extremadamente incomodo. La crema de la invencion es tambien estable y no se escurre mientras que los productos del arte previo en forma de soluciones o geles se escurren facilmente sobre la superficie de la piel por la gravedad y afectan a la piel adyacente a la lesion que esta siendo tratada.experts The cream of the invention does not cause pain and at most causes a slight stinging sensation while the prior art formulation stings and produces abrasion to a large extent and can be extremely uncomfortable. The cream of the invention is also stable and does not drain while prior art products in the form of solutions or gels easily drain onto the surface of the skin due to gravity and affect the skin adjacent to the lesion being treated. .
La crema de la invencion puede tambien ser facilmente envasada en pequenos envases tales como tubos que permiten una facil dispensacion de pequenas cantidades de la crema, mientras que las formulaciones del arte previo se envasan generalmente en botellas desde las que las soluciones no se dispensan con facilidad. La crema de la invencion tampoco es peligrosa si se derrama, mientras que las formulaciones del arte previo son lfquidos acidos potencialmente erosivos. La piel que rodea la lesion puede entrar en contacto con la crema de la invencion, pero debido a la baja concentracion de acido tricloroacetico en la crema, la piel circundante no se ve afectada mientras que las formulaciones del arte previo danan la piel circundante, causa la muerte de celulas y una descamacion potencialmente profunda. Debido a que la piel circundante esta protegida por sus propiedades de barrera superficial del estrato corneo (capa cornea), que no se destruyen por la baja concentracion de acido tricloroacetico, las celulas de la capa de queratinocitos basales (creciente) de la epidermis (capa superior de la piel) no se destruyen y de ese modo se acelera el proceso de curacion. Concentraciones mas elevadas de acido tricloroacetico, segun se observa en las formulaciones del arte previo, destruyen la barrera de la epidermis y permiten el dano a la capa mas profunda de las celulas crecientes y retrasan la curacion.The cream of the invention can also be easily packaged in small packages such as tubes that allow easy dispensing of small amounts of the cream, while prior art formulations are generally packaged in bottles from which solutions are not readily dispensed. . The cream of the invention is also not dangerous if spilled, while the formulations of the prior art are potentially erosive acidic liquids. The skin surrounding the lesion may come into contact with the cream of the invention, but due to the low concentration of trichloroacetic acid in the cream, the surrounding skin is not affected while the prior art formulations damage the surrounding skin, cause the death of cells and a potentially deep peeling. Because the surrounding skin is protected by its surface barrier properties of the stratum corneum (corneal layer), which is not destroyed by the low concentration of trichloroacetic acid, the cells of the basal keratinocyte (growing) layer of the epidermis (layer upper skin) are not destroyed and thus the healing process is accelerated. Higher concentrations of trichloroacetic acid, as seen in prior art formulations, destroy the epidermis barrier and allow damage to the deepest layer of growing cells and delay healing.
La crema de la invencion es estable durante al menos un ano y de ese modo se presta a la venta sin prescripcion medica, mientras que las formulaciones del arte previo tales como la formulacion descrita en Mezzoli, son inestables si la concentracion de acido tricloroacetico es menor del 30%. Ademas, el tiempo de accion es de cuatro a cinco minutos para la crema, mientras que para las formulaciones del arte previo con altas concentraciones el tiempo de exposicion se mide en segundos. Incluso si la crema de la invencion se usa de forma incorrecta, por ejemplo, se deja en la piel durante diez minutos, el solicitante ha observado que tampoco hay efectos perjudiciales. Si se utilizan formulaciones del arte previo tales como la de Mezzoli para “doble” exponer la piel, pueden surgir graves complicaciones y dicha exposicion puede tener como resultado graves cicatrices.The cream of the invention is stable for at least one year and thus lends itself to the sale without medical prescription, while prior art formulations such as the formulation described in Mezzoli are unstable if the concentration of trichloroacetic acid is lower. of 30%. In addition, the action time is four to five minutes for the cream, while for prior art formulations with high concentrations the exposure time is measured in seconds. Even if the cream of the invention is used incorrectly, for example, it is left on the skin for ten minutes, the applicant has observed that there are no harmful effects either. If prior art formulations such as that of Mezzoli are used to "double" expose the skin, serious complications may arise and such exposure may result in severe scarring.
La crema de la invencion requiere generalmente una unica aplicacion, despues de la cual la lesion se seca y generalmente no es necesario que la crema se utilice en dfas sucesivos. Las formulaciones del arte previo requieren de uno a tres tratamientos por dfa hasta que se cura la herid y este proceso tiene una duracion de dos a cuatro dfas. En el proceso de curacion de la invencion, la lesion se seca y apenas se descama, mientras que en el caso de las formulaciones del arte previo la descamacion es un componente significativo de la fase de curacion. Ademas, la crema de la invencion no requiere un tipo especffico de aplicador y puede aplicarse facilmente con la punta del dedo, mientras que la formulacion del arte previo descrita por Mezzoli requiere un tipo especffico de aplicador (ver por ejemplo las reivindicaciones 12, 13 y 14 de Mezzoli).The cream of the invention generally requires a single application, after which the lesion dries and it is generally not necessary for the cream to be used in successive days. The prior art formulations require one to three treatments per day until the wound is healed and this process lasts two to four days. In the process of healing the invention, the lesion dries and barely peels, while in the case of prior art formulations, peeling is a significant component of the healing phase. In addition, the cream of the invention does not require a specific type of applicator and can be easily applied with the fingertip, while the prior art formulation described by Mezzoli requires a specific type of applicator (see for example claims 12, 13 and 14 of Mezzoli).
La invencion se describe a continuacion a modo de ejemplo en referencia a los siguientes Ejemplos.The invention is described below by way of example in reference to the following Examples.
Ejemplo 1Example 1
En diferentes realizaciones de la invencion, los geles o cremas se prepararon utilizando acido tricloroacetico (de 1% a 5% m/m), los agentes quelantes EDTA disodico o diacetato de tetrasodio glutamato (de 0,05 a 2% m/m), el emulsionante estearato de glicerilo (de 0,5 a 10% m/m) o los emulsionantes alcohol cetearflico, estearato de glicerilo, estearato de PEG-40 y ceteareth-20 (de 1 a 10% m/m), el formador de viscosidad goma xantana (de 0,1 a 1% m/m), los humectantes propilenglicol (de 0,5 a 5% m/m) y agua (al 100%). El dicacetato de tetrasodio glutamato puede obtenerse en comercios.In different embodiments of the invention, gels or creams were prepared using trichloroacetic acid (1% to 5% m / m), EDTA disodium chelating agents or tetrasodium glutamate diacetate (0.05 to 2% m / m) , the emulsifier glyceryl stearate (0.5 to 10% m / m) or the emulsifiers cetearyl alcohol, glyceryl stearate, PEG-40 stearate and ceteareth-20 (1 to 10% m / m), the former of xanthan gum viscosity (0.1 to 1% m / m), propylene glycol humectants (0.5 to 5% m / m) and water (100%). Tetrasodium glutamate dicacetate can be obtained in stores.
Para la elaboracion de la crema, los componentes se pesaron en una bascula digital calibrada. Dependiendo del tamano del lote, se utilizo una balanza Mettler de Meltter Toledo modelo PB 3002-5 para los lotes mas pequenos. Los diversos componentes se mezclaron en recipientes de acero inoxidable o cubetas de plastico.For the elaboration of the cream, the components were weighed in a calibrated digital scale. Depending on the size of the lot, a Mettler scale from Meltter Toledo model PB 3002-5 was used for smaller lots. The various components were mixed in stainless steel containers or plastic buckets.
La goma xantana y el propilenglicol se mezclaron en primer lugar para formar una pasta y la pasta se anadio a una parte del agua y se mezclo completamente con un homogeneizador Silverson para hidratar la goma xantana. Estearato de glicerilo y estearato de PEG-100 y alcohol cetearflico, estearato de glicerilo, estearato de PEG-40 y ceteareth-20 se pesaron y calentaron en una placa calentada a 80°C en un recipiente de acero inoxidable con fondo de cobre. Se utilizo un termometro digital para medir la temperatura.Xanthan gum and propylene glycol were first mixed to form a paste and the paste was added to a part of the water and mixed thoroughly with a Silverson homogenizer to hydrate the xanthan gum. PEG-100 glyceryl stearate and cetearyl alcohol, glyceryl stearate, PEG-40 stearate and ceteareth-20 were weighed and heated on a 80 ° C heated plate in a copper-bottomed stainless steel vessel. A digital thermometer was used to measure the temperature.
Se anadio agente quelante, EDTA disodico y los emulsionantes estearato de glicerilo, alcohol cetearflico, estearato de glicerilo, estearato de PEG-40 y ceteareth-20 al volumen de agua a 80°C, y se homogeneizo con un homogeneizador Silverson a alta velocidad (habitualmente de 50.000 a 60.000 rpm) durante 2-5 minutos segun el tamano del lote para producir una emulsion. La goma se anadio a la emulsion y la mezcla se homogeneizo a velocidad media (habitualmente aproximadamente a 25.000 rpm) para producir un material homogeneo.Chelating agent, disodium EDTA and the emulsifiers of glyceryl stearate, cetearyl alcohol, glyceryl stearate, PEG-40 stearate and ceteareth-20 were added to the volume of water at 80 ° C, and homogenized with a Silverson homogenizer at high speed ( usually from 50,000 to 60,000 rpm) for 2-5 minutes depending on the size of the batch to produce an emulsion. The gum was added to the emulsion and the mixture was homogenized at medium speed (usually at approximately 25,000 rpm) to produce a homogeneous material.
El material se dejo enfriar de forma natural hasta <50°C. Se anadio el ingrediente activo acido tricloroacetico, disuelto en una cantidad igual de agua fna, mientras que se homogeneizo a una velocidad media (habitualmente a 25.000 rpm) hasta que la mezcla se puso brillante.The material was allowed to cool naturally to <50 ° C. The active ingredient trichloroacetic acid, dissolved in an equal amount of fine water, was added while homogenizing at medium speed (usually at 25,000 rpm) until the mixture became bright.
Ejemplo 2Example 2
5 Tratamiento del Herpes I (Herpes Simple) y Herpes II (Herpes genital)5 Treatment of Herpes I (Herpes Simplex) and Herpes II (Genital Herpes)
El area de la piel afectada se limpio y la crema que contema un 2,5% de acido tricloroacetico preparada tal como se describe en el Ejemplo 1, se aplico en una pequena cantidad del tamano de un guisante (de mayor tamano para lesiones mas extensas) para cubrir el area infectada. La crema se aplico en una cantidad suficiente para producir una capa opaca de color blanco sobre la lesion. La crema se dejo en la piel durante 4 minutos y a continuacion se 10 lavo con agua. Las lesiones cambiaron de forma significativa secando y produciendo una ligera costra. Si fuera necesario, las lesiones se trataron nuevamente de la misma forma despues de un periodo de 24 horas.The affected skin area was cleaned and the cream containing 2.5% prepared trichloroacetic acid as described in Example 1 was applied in a small amount of the size of a pea (larger size for more extensive lesions ) to cover the infected area. The cream was applied in an amount sufficient to produce an opaque white layer on the lesion. The cream was left on the skin for 4 minutes and then washed with water. The lesions changed significantly drying and producing a slight scab. If necessary, the lesions were treated again in the same way after a 24-hour period.
Ejemplo 3Example 3
Tratamiento del Herpes ZosterHerpes Zoster Treatment
El area de la piel afectada se limpio y la crema que contema un 2,5% de acido tricloroacetico preparada segun se 15 describe en el Ejemplo 1, se aplico con una brocha suave para cubrir el area infectada. La crema se dejo en la piel durante 4-10 minutos y a continuacion se lavo con agua. Las lesiones cambiaron significativamente secandolas. Las lesiones se trataron nuevamente de la misma forma despues de un periodo de 24 horas. Si hubo un cambio mmimo en las lesiones y permanecieron incomodas, se volvio a realizar una aplicacion despues de 12 horas de y a continuacion otra vez despues de 24 horas. Los tratamientos se repitieron a diario hasta que fue evidente que la 20 lesion se hubo estabilizado. Generalmente se necesito un maximo de cuatro dfas para el herpes Zoster.The affected skin area was cleaned and the cream containing 2.5% trichloroacetic acid prepared as described in Example 1, was applied with a soft brush to cover the infected area. The cream was left on the skin for 4-10 minutes and then washed with water. The lesions changed significantly by drying them. The lesions were treated again in the same way after a 24-hour period. If there was a minimal change in the lesions and they remained uncomfortable, an application was reapplied after 12 hours of and then again after 24 hours. The treatments were repeated daily until it was evident that the lesion had stabilized. Generally, a maximum of four days is needed for herpes Zoster.
Claims (12)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ZA201102483 | 2011-04-04 | ||
ZA201102483 | 2011-04-04 | ||
PCT/IB2012/051483 WO2012137106A1 (en) | 2011-04-04 | 2012-03-28 | The treatment of viral infections |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2615236T3 true ES2615236T3 (en) | 2017-06-06 |
Family
ID=45999912
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES12716630.4T Active ES2615236T3 (en) | 2011-04-04 | 2012-03-28 | Treatment of viral infections |
Country Status (16)
Country | Link |
---|---|
US (2) | US9226908B2 (en) |
EP (1) | EP2694033B1 (en) |
KR (1) | KR20140041476A (en) |
CN (1) | CN103442692B (en) |
AU (1) | AU2012241013B2 (en) |
CA (1) | CA2829181C (en) |
DK (1) | DK2694033T3 (en) |
ES (1) | ES2615236T3 (en) |
MY (1) | MY168692A (en) |
PL (1) | PL2694033T3 (en) |
PT (1) | PT2694033T (en) |
RU (1) | RU2545918C1 (en) |
SG (1) | SG192966A1 (en) |
UA (1) | UA107155C2 (en) |
WO (1) | WO2012137106A1 (en) |
ZA (1) | ZA201306342B (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG192966A1 (en) | 2011-04-04 | 2013-09-30 | Environ Skin Care Pty Ltd | The treatment of viral infections |
US10109908B2 (en) | 2014-04-04 | 2018-10-23 | Samsung Electronics Co., Ltd. | Antenna module and electronic devices comprising the same |
KR101666196B1 (en) * | 2015-12-09 | 2016-10-14 | (주)아인스코퍼레이션 | Clean gel composite for antibacterial and antiviral and deodorization and the process of manufacture |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5827884A (en) | 1995-09-15 | 1998-10-27 | Omp Acquisition Corporation | Skin peel maintenance composition and method |
IT1312313B1 (en) | 1999-05-24 | 2002-04-15 | Giorgio Mezzoli | TRICHLOROACETIC ACID FOR THE PREPARATION OF SOLUTIONS AND / OCOMPOSITIONS FOR THE TREATMENT OF EROSIVE AND / OR ULCERATIVE INJURIES. |
CN1365664A (en) * | 2002-01-23 | 2002-08-28 | 王怀琛 | Medicine for removing vegetation from human body and its preparing process and application |
US6899890B2 (en) | 2002-03-20 | 2005-05-31 | Kv Pharmaceutical Company | Bioadhesive drug delivery system |
US20060263398A1 (en) | 2005-05-23 | 2006-11-23 | Kalil Enterprises, L.L.P. | Method and compound for skin chemical peel |
EP2144590B1 (en) * | 2007-05-14 | 2018-08-01 | Sytheon Ltd. | Skin treatment compositions and methods |
SG192966A1 (en) | 2011-04-04 | 2013-09-30 | Environ Skin Care Pty Ltd | The treatment of viral infections |
-
2012
- 2012-03-28 SG SG2013064779A patent/SG192966A1/en unknown
- 2012-03-28 ES ES12716630.4T patent/ES2615236T3/en active Active
- 2012-03-28 US US14/005,650 patent/US9226908B2/en active Active
- 2012-03-28 RU RU2013148939/15A patent/RU2545918C1/en active
- 2012-03-28 CN CN201280014642.6A patent/CN103442692B/en active Active
- 2012-03-28 KR KR1020137029054A patent/KR20140041476A/en not_active Application Discontinuation
- 2012-03-28 PT PT127166304T patent/PT2694033T/en unknown
- 2012-03-28 AU AU2012241013A patent/AU2012241013B2/en active Active
- 2012-03-28 PL PL12716630T patent/PL2694033T3/en unknown
- 2012-03-28 UA UAA201311638A patent/UA107155C2/en unknown
- 2012-03-28 MY MYPI2013003645A patent/MY168692A/en unknown
- 2012-03-28 WO PCT/IB2012/051483 patent/WO2012137106A1/en active Application Filing
- 2012-03-28 CA CA2829181A patent/CA2829181C/en active Active
- 2012-03-28 DK DK12716630.4T patent/DK2694033T3/en active
- 2012-03-28 EP EP12716630.4A patent/EP2694033B1/en active Active
-
2013
- 2013-08-22 ZA ZA2013/06342A patent/ZA201306342B/en unknown
-
2015
- 2015-11-30 US US14/954,607 patent/US9901555B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
NZ614958A (en) | 2015-05-29 |
US20160081953A1 (en) | 2016-03-24 |
AU2012241013B2 (en) | 2015-08-06 |
PT2694033T (en) | 2017-02-21 |
CA2829181C (en) | 2016-01-05 |
UA107155C2 (en) | 2014-11-25 |
EP2694033A1 (en) | 2014-02-12 |
DK2694033T3 (en) | 2017-03-20 |
EP2694033B1 (en) | 2016-12-14 |
US9901555B2 (en) | 2018-02-27 |
KR20140041476A (en) | 2014-04-04 |
US9226908B2 (en) | 2016-01-05 |
SG192966A1 (en) | 2013-09-30 |
AU2012241013A1 (en) | 2013-09-12 |
ZA201306342B (en) | 2014-04-30 |
CN103442692A (en) | 2013-12-11 |
WO2012137106A1 (en) | 2012-10-11 |
CN103442692B (en) | 2016-05-18 |
CA2829181A1 (en) | 2012-10-11 |
MY168692A (en) | 2018-11-29 |
US20140011874A1 (en) | 2014-01-09 |
WO2012137106A8 (en) | 2013-10-24 |
RU2545918C1 (en) | 2015-04-10 |
PL2694033T3 (en) | 2017-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Siddiqui et al. | Management of radiation toxicity in head and neck cancers | |
ES2278393T3 (en) | ANTIMICROBIAL TREATMENT OF VIRUS HERPES SIMPLEX AND OTHER INFECTIOUS DISEASES. | |
ES2396719T3 (en) | Composition for treatment of skin lesions | |
CN105307647B (en) | For treating the sterilizing oral composition of portacaval mucositis | |
Akerzoul et al. | Low laser therapy as an effective treatment of recurrent aphtous ulcers: a clinical case reporting two locations | |
TWI841523B (en) | Methods of treating and/or preventing actinic keratosis | |
ES2621849T3 (en) | Method of treatment or improvement of mucocutaneous or ocular toxicities. | |
JP7096332B2 (en) | Compositions for use in the prevention and / or treatment of tumor treatment-induced oral gastrointestinal mucositis | |
ES2748805T3 (en) | Improved wound healing compositions comprising microspheres | |
ES2615236T3 (en) | Treatment of viral infections | |
ES2729373T3 (en) | Topical antifungal composition to treat onychomycosis | |
ES2240987T3 (en) | THERAPEUTIC COMPOSITION FOR EXTERNAL USE CONTAINING ADRENAL CORTICOESTEROIDS FOR THE TREATMENT OF DERMATITIS. | |
US9144612B2 (en) | Dermatological compositions containing an association of peroxide lipids and zinc, and uses thereof in particular in the treatment of labial and/or genital herpes | |
ES2379474T3 (en) | Dermatological product for the treatment and / or skin care with neurodermitis | |
ES2694623T3 (en) | Treatment or prevention of seborrheic keratosis using artemisinin and derivatives thereof | |
ES2255988T3 (en) | USE OF A WATER OIL EMULSION FOR THE PREPARATION OF A MEDICINAL PRODUCT. | |
WO2017220845A1 (en) | Compositions for the treatment of ischemic ulcers and stretch marks | |
NZ606177A (en) | Compositions for the treatment of actinic keratosis | |
WO2011057363A1 (en) | Disposable device and uses thereof for skin and mucosal applications | |
ES2491693T3 (en) | Agent for the treatment of skin conditions | |
NZ614958B2 (en) | The treatment of viral infections | |
Pilania et al. | Ozone therapy–a milestone in dentistry; a review | |
US11813237B2 (en) | Creatine, its derivatives, compositions and methods of use thereof | |
Gori et al. | Paradoxical effect of infliximab in a patient with hidradenitis suppurativa. | |
RU2179841C1 (en) | Method for treating the cases of parodontosis |